한빛사 논문
Eunyoung Choi1,2,3,*, Tyler L Lantz4, Gregory Vlacich5, Theresa M Keeley6, Linda C Samuelson6, Robert J Coffey1,3,7,8,9, James R Goldenring1,2,7,3,8, Anne E Powell4,*
1Nashville VA Medical Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
2Section of Surgical Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
3Epithelial Biology Center, Nashville, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
4Department of Biology, Institute of Molecular Biology, University of Oregon, Oregon, USA
5Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
6Department of Molecular & Integrative Physiology, The University of Michigan, Michigan, USA
7Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
8Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
9Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Correspondence to : Eunyoung Choi, Epithelial Biology Center and Section of Surgical Science Vanderbilt University Medical Center 10425-D MRB IV 2213 Garland Avenue Nashville, TN 37232; and Dr Anne E Powell, Department of Biology, Institute of Molecular Biology, University of Oregon 218 Streisinger Hall 1370 Franklin Blvd Eugene, OR 97405
Abstract
Objective
Lrig1 is a marker of proliferative and quiescent stem cells in the skin and intestine. We examined whether Lrig1-expressing cells are long-lived gastric progenitors in gastric glands in the mouse stomach. We also investigated how the Lrig1-expressing progenitor cells contribute to the regeneration of normal gastric mucosa by lineage commitment to parietal cells after acute gastric injury in mice.
Design
We performed lineage labelling using Lrig1-CreERT2/+;R26R-YFP/+ (Lrig1/YFP) or R26R-LacZ/+ (Lrig1/LacZ) mice to examine whether the Lrig1-YFP-marked cells are gastric progenitor cells. We studied whether Lrig1-YFP-marked cells give rise to normal gastric lineage cells in damaged mucosa using Lrig1/YFP mice after treatment with DMP-777 to induce acute injury. We also studied Lrig1-CreERT2/CreERT2 (Lrig1 knockout) mice to examine whether the Lrig1 protein is required for regeneration of gastric corpus mucosa after acute injury.
Results
Lrig1-YFP-marked cells give rise to gastric lineage epithelial cells both in the gastric corpus and antrum, in contrast to published results that Lgr5 only marks progenitor cells within the gastric antrum. Lrig1-YFP-marked cells contribute to replacement of damaged gastric oxyntic glands during the recovery phase after acute oxyntic atrophy in the gastric corpus. Lrig1 null mice recovered normally from acute gastric mucosal injury indicating that Lrig1 protein is not required for lineage differentiation. Lrig1+ isthmal progenitor cells did not contribute to transdifferentiating chief cell lineages after acute oxyntic atrophy.
Conclusions
Lrig1 marks gastric corpus epithelial progenitor cells capable of repopulating the damaged oxyntic mucosa by differentiating into normal gastric lineage cells in mouse stomach.
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